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Evaluation of antitumor potential of an anti-glypican-1 monoclonal antibody in preclinical lung cancer models reveals a distinct mechanism of action.

ABSTRACT:

Aim

The main objective of this study was to investigate the antitumor effect of a mouse anti-human glypican-1 (GPC1) monoclonal antibody (mAb) on non-small cell lung carcinoma (NSCLC) and associated molecular mechanisms.

Methods

The anti-proliferative and anti-migratory activities of anti-GPC1 mAb were examined in A549 and H460 NSCLC cells and LL97A lung fibroblasts. The inhibitory effect of anti-GPC1 mAb on tumor growth was evaluated in an orthotopic lung tumor model.

Results

The in vitro study showed that anti-GPC1 mAb profoundly inhibited the anchorage-independent growth of A549 and H460 NSCLC cells and exhibited relatively high cytotoxic activities towards LL97A lung fibroblasts, A549/LL97A and H460/LL97A coculture spheroids. Moreover, anti-GPC1 mAb significantly decreased the expression of phospho-Src (p-Src; Tyr416), p-Akt (Ser473) and β-catenin in the co-cultured LL97A lung fibroblasts, and the expression of phospho-mitogen-activated protein kinase kinase (p-MEK; Ser217/221) and phospho-90 kDa ribosomal s6 kinase (p-p90RSK; Ser380) in co-cultured A549 cells. When anti-GPC1 mAb was administered to tumor-bearing mice, the inhibitory effect of anti-GPC1 mAb on the orthotopic lung tumor growth was not statistically significant. Nonetheless, results of Western blot analysis showed significant decrease in the phosphorylation of fibroblast growth factor receptor 1 (FGFR1) at Tyr766, Src at Tyr416, extracellular signal-regulated kinase (ERK) at Thr202/Tyr204, 90 kDa ribosomal S6 kinase (RSK) at Ser380, glycogen synthase kinases 3α (GSK3α) at Ser21 and GSK3β at Ser9 in tumor tissues. These data implicate that anti-GPC1 mAb treatment impairs the interaction between tumor cells and tumor associated fibroblasts by attenuating the paracrine FGFR signal transduction.

Conclusions

The relatively potent cytotoxicity of anti-GPC1 mAb in lung fibroblasts and its potential inhibitory effect on the paracrine FGFR signal transduction warrant further studies on the combined use of this mAb with targeted therapeutics to improve therapeutic outcomes in lung cancer.

SUBMITTER: Li M

PROVIDER: S-EPMC11220310 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Evaluation of antitumor potential of an anti-glypican-1 monoclonal antibody in preclinical lung cancer models reveals a distinct mechanism of action.

Li Minghua M Wang Yanhong Y Lin Xiaoyang X Yang Haiqiang H Zhang Xiaolin X Bai Yun Y Li Xiankun X Zhang Lulu L Cheng Feng F Cao Chuanhai C Zhou Qingyu Q

Exploration of targeted anti-tumor therapy 20240617 3

<h4>Aim</h4>The main objective of this study was to investigate the antitumor effect of a mouse anti-human glypican-1 (GPC1) monoclonal antibody (mAb) on non-small cell lung carcinoma (NSCLC) and associated molecular mechanisms.<h4>Methods</h4>The anti-proliferative and anti-migratory activities of anti-GPC1 mAb were examined in A549 and H460 NSCLC cells and LL97A lung fibroblasts. The inhibitory effect of anti-GPC1 mAb on tumor growth was evaluated in an orthotopic lung tumor model.<h4>Results< ...[more]

PMID: 38966167

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Dataset Information

Evaluation of antitumor potential of an anti-glypican-1 monoclonal antibody in preclinical lung cancer models reveals a distinct mechanism of action.

Aim

Methods

Results

Conclusions

Publications

Evaluation of antitumor potential of an anti-glypican-1 monoclonal antibody in preclinical lung cancer models reveals a distinct mechanism of action.

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